Microelectronic components and electronic networks comprising DNA

ABSTRACT

A microelectronic network is fabricated on a fibrous skeleton by binding or complexing electronically functional substances to the nucleic acid skeleton. The skeleton comprises fibers with nucleotide chains. The assembly of the fibers into a network is based on interactions of nucleotide chain portions of different fibers.

FIELD OF THE INVENTION

The present invention is generally in the field of electronics andrelates to electronic networks and circuits as well as to components andjunctions of such networks or circuits.

PRIOR ART

Prior art believed to be relevant as background of the invention as wellas to manufacture or experimental techniques described herein is listedbelow:

-   1. Averin, D. V. and Likharev, K. K., in Mesoscopic Phenomena in    Solids, eds. Altshuler B., Lee P., and Webb, R., Elsevier,    Amsterdam, p. 173, 1991.-   2. Grabert H., and Devoret M., eds., Single Charge Tunneling,    Plenum, New York, 1992.-   3. Kastner, M. A., Rev. Mod. Phys. 64:849, 1992.-   4. Porath, D. and Milloh, O., J. Appl. Phys., 85:2241, 1997.-   5. Meirav, U. and Foxman, E. B., Semiconductor Science and    Technology, 11:255, 1996.-   6. Kouwenhoven, L. P. et al., Proceedings of the Advanced Study    Institute on Mesoscopic Electron Transport. Kouwenhoven, L. P.,    Schon, G., and Sohn, L. L. eds., Kluwer, 1997.-   7. Langer, L., et al., Phys. Rev. Lett., 76, 479, 1996.-   8. Lehn, J. M., Supramolecular Chemistry: Concepts and Perspectives,    VCH, Weinheim, 1995.-   9. Austin, R. J., et al., Phys. Rev. Lett., 50:32, 1997.-   10. Bensimon, D., et al., Phys. Rev. Lett., 74:4754, 1995.-   11. Bensimon A., et al., Science, 265:2096, 1994.-   12. Wirtz, D., Phys. Rev. Lett., 75:2436, 1995.-   13. Zimmermann, R. M., and Cox, E. C., Nucleic Acids Research,    22:492, 1994.-   14. Mirkin, C. A., et al., Nature, 382:607, 1996.-   15. Alivisatos, A. P., et al., Nature, 382609: 1996.-   16. Coffer, J. L., et al., Appl. Phys. Lett., 69(25):3851, 1996.-   17. Hollenberg, et al., U.S. Pat. No. 5,561,071.-   18. Hall, B. D., Holmlin, R. E., and Barton, K., Nature, 382:731,    1996.-   19. Barton, J. K., in Bioinorganic Chemistry, eds. Bertini, I., et    al., University Science Books, Mill Avalley, 1994.-   20. Spiro T. G., ed., Nucleic Acid—Metal Ion Interactions, Wiley    Interscience, New York, 1980.-   21. Marzilli, L. G., Kistenmacher, T. J., and Rossi, M., J. Am.    Chem. Soc., 99:2797, 1977.-   22. Eichorn, G. L., ed., Inorganic Biochemistry, Vol. 2, Elsevier,    Press, Amsterdam, Ch. 33-34, 1973.-   23. Roberts, W. J., Proc. R. Acad. (Amsterdam) 38:540, 1935.-   24. Holgate, C. S., et al., The J. of Histochemistry and    Cytochemistry, 31:938, 1983.-   25. Danscher, G., and Norgaard, J. O. R., ibid., 31:1394, 1983.-   26. Burroughes, J. H., et al., Nature, 347:539, 1990.-   27. J. E. Mueller, S. M. Du and N. C. Seeman, J. Am. Chem. Soc.,    113:6306-6308, 1991.-   28. S. M. Du, and N. C. Seeman, J. Am. Chem. Soc., 114:9652-9655,    1992.-   29. N. C. Seeman, J. Chen, S. M. Du, J. E. Mueller, Y. Zhang, T. J.    Fu, Y. Wang and S. Zhang, New J. Chem., 17:739-755, 1993.-   30. N. R. Kallenbach, R. I. Ma and N. C. Seeman, Nature,    305:829-831, 1983.-   31. A. Goffeau, Nature, News and Views, 385:202-203, 1997.-   32. G. B. Birrell, D. L. Habliston, K. K. Hedberg and O. H.    Griffith, J. Histochem. Cytochem, 34:339, 1986.-   33. G. Danscher. Histochemistry, 71:81, 1981.-   34. L. Scopsi and L-I Larsson, Histochemistry, 82:321, 1985.-   35. L. Scopsi and L-I Larsson, Medical Biology, 64:139, 1986.-   36. D. R. Springall, G. W. Hacker, L. Grimelius and J. M. Polak,    Histochemistry, 81:603, 1984.-   37. J. Teasdale, P. Jackson, C. S. Holgate and P. N. Cowen,    Histochemistry, 87:185, 1987.

Acknowledgement of these references will be made by indicating thesenumbers from the above list.

BACKGROUND OF THE INVENTION

The miniaturization of microelectronics and logics, at currenttechnology, is approaching its practical and theoretical limits. Variousdesign and operational considerations such as heat removal,heterogeneity, connectivity as well as present photolitographictechniques restrict the practical size of minimal feature in present,semiconductor-based electronic components to about 0.25-0.3 μm. It isclear that further miniaturization of electronic components must involvenew approaches and concepts for the fabrication of the electroniccomponents and logic circuits.

Nanometer scale electronics needs to consider two fundamental issues:operating principles of the corresponding electronic components andschemes to fabricate such components and their integration into usefulcircuits.

A number of operation principles have been suggested based on chargingeffects⁽¹⁻⁶⁾ which become increasingly prominent as the devicedimensions diminish. The construction of nanoscale circuits cannot beimplemented by existing microelectronics technology. In particular,inter element wiring and electrical interfacing to the macroscopic worldbecome increasingly problematic. Molecular recognition processes andself-assembly of molecules into supramolecular assemblies may be usedfor the construction of complex structure⁽⁵⁾. However, integratingelectronic materials with these structures, or providing them withelectronic functionality, has not yet been attained.

Nucleic acids possess self-assembly properties which can be used to formnetworks of nucleic acid fibers⁽²⁷⁻³⁰⁾. DNA has already been employed asan organizer of nano structures in the assembly of colloidal particlesinto macroscopic crystal-like aggregates^((14.15)) and in dictating theshape of semiconductor nano particle assemblies^((16,17)).

Glossary

In the following, use will be made with some terms, which terms andtheir meaning in the context of the invention are as follows:

-   Nucleotide chain—A sequence of nucleotides. The nucleotides may be    ribonucleotides, deoxyribo-nucleotides, other ribo nucleotide    derivatives, a variety of synthetic, i.e. non naturally occurring    nucleotides e.g. peptide nucleic acid (PNA), as well as any    combination of the above. The nucleotide chain may be    single-stranded, double-stranded or multi-stranded.-   Fiber—an elongated threadlike component. A fiber may have a    polymeric or co-polymeric skeleton or may comprise stretches of    different polymers or co-polymers linked to one another. A fiber may    be chemically modified by depositing thereon one or more substances    or particles. The fibers of the invention comprises at least one    nucleotide chain. The fibers of the invention may also consist of    nucleotide chains only.-   Binding—A term to refer collectively to all types of interactions    which bind together two or more molecules, substances, particles,    supramolecular structures, etc., or brings to binding of these to a    solid substrate. The binding may be covalent or non-covalent binding    (non-covalent binding may include one or more of ionic interaction,    hydrophobic interaction, Van der Waals interaction, chemical    sorption, etc.). Derivation of this term (i.e. “bind”, “bound”,    etc.) will have meanings commensurate to that of “binding”,    depending on the syntax.-   Interaction—non-covalent binding of two molecular entities.    Derivation of this term (i.e. “interact”, “interacting”, etc.) will    have meanings commensurate to that of “interaction”, depending on    the syntax.-   Functionalized nucleotide chain—A nucleotide chain which has been    chemically or physically modified or attached with a substance,    molecule, clusters of atoms or molecules or particles deposited    thereon which impart electric or electronic properties to the    nucleotide chain. Such substances or particles may be bound to the    nucleotide chain by a variety of interactions (e.g. may be    chemically deposited on the chain, may be complexed thereon by a    variety of chemical interactions, may be associated with the chain    by electrostatic or hydrophobic interactions, etc.). The substances    or particles may be bound to the nucleotide chain based on the    general chemical properties of the chain or may be bound to the    nucleotide chain in a sequence specific manner. Examples of such    substances, molecules, clusters or particles are: metal e.g. which    gives rise to a conductive nucleotide chain; a variety of    semi-conductive materials which can form conductors (or resistors),    electronic p/n junctions, and others; molecules, clusters of    molecules or particles which can be associated with the nucleotide    chain to form functional logic junctions between nucleotide chains;    etc. Depending on the type of bound substances or particles, the    electric or electronic properties imparted to the nucleotide chain    may be conduction, insulation, gating, switching, electrical    amplification, etc.-   Functionalized fiber—a fiber which has been chemically or physically    modified or attached with substances, clusters of atoms or molecules    or particles deposited thereon which impart electric or electronic    properties to the fiber or a part thereof. An example of a    functionalized fiber is a fiber whose nucleotide chain has been    functionalized.-   Junction—A point of connection of two or more fibers to one another.    Examples of junctions can be seen in FIGS. 2A-2F (please refer to    the description below relating to this figure).-   Network—A geometrical one, two or three-dimensional structure which    comprises at least one fiber and may comprise other components such    as particles, molecules, e.g. proteins, other macromolecules and    supramolecular complexes, etc. The term “network” may refer to the    geometrical arrangement of the fibers and junctions between them.    This term may also be used, at times, to refer to a functionalized    network (see below).-   Functionalized network—a network comprising at least one    functionalized fiber. The functionalized network has properties    defined among others, by its geometry, the type of connectivities    and junctions between different fibers, by the nature of the    deposited or complexed substances or particles, etc.-   Electronic functionality (or electronically functional)—A property    of a component which renders it to serve as an electronic component.-   Interface component—A conducting substrate, which may be made of    metal or of any other conducting material or coated by metal or such    conducting material, which serves for connection of said network to    external electronic or electric components or circuitry, thus    serving as an input/output (I/O) interface with an external    component or circuitry. The interface components are linked to the    network on the one hand and are electrically linked to an external    component or circuitry, on the other hand. The interface component,    may at times also be referred to herein as “electrode”.-   Wire—In the context of the invention—a functionalized fiber with    bound substance or particles which give rise to electric    conductivity along the fiber. The wires are conducting components    which may interconnect two or more sites of the network, connect the    network with an electrode, connect between two networks, etc. A wire    may extend an entire length of a functionalized fiber or may extend    only part of the length of a functionalized fiber, with other parts    serving as base for various types of electronic components, e.g. a    diode, an electric switch, etc.-   Insulator—A component of a network which acts as a barrier for    electric conduction.-   Conductor—a component of a network which permits change transfer    therethrough.-   Switch—A two or multi terminal component where the conductance    between any pair of terminals can be turned on or off by a control    signal including, for example, the potential at another terminal,    light, pressure, chemical reaction, stress, etc.-   Electronic component—Any component which may form part of an    electronic network other than a wire or a simple junction between    wires (a simple junction being a junction having the purpose of only    providing a link between fibers or functionalized fibers). An    electronic component may be a conductor, an insulator, a switch, a    transistor, a diode, a light emitting diode, a capacitor, an    inductor, and others.-   Network component—a term referring collectively both to a wire and    to an electronic component.-   External circuitry, external component—An electronic or electric    circuitry or an electronic or electric component, respectively,    situated electrically external to the network and typically    comprises prior art electric or electronic components, including    standard solid-state microelectronic components.-   Linker—An agent (molecule, complex of molecules, supermolecular    structure, macromolecule, aggregate, colloid particle, molecular    cluster, etc.) that acts in providing a physical link between    network components or between the network and the interface    component. The linkers may have chemical groups for covalent or non    covalent binding, (e.g. complexation or sorption, etc.) to the    network components or to the interface component. Examples of a    linker are: a nucleic acid binding protein; synthetic molecules with    a binding ability to a specific nucleic acid sequence; a short,    single or multiple stranded nucleic acid sequences (e.g. an    oligonucleotide), e.g. having a “sticky end” and being modified at    its other end, to allow it binding to the interface component; a    group comprising one member of a binding couple for binding to    another group or component carrying the other member of the binding    couple (a binding couple being a pair of molecules which    specifically interact with one another such as antigen-antibody    receptor-ligand, biotin-avidin, sugar-lectins, nucleotide    sequence-complementary sequence, etc.).-   Complexing agent—An agent which is used for binding of components of    the network to one another. The binding may be covalent or non    covalent. Examples of complexing agents are: proteins with a    specific binding ability to a nucleic acid sequence;    oligonucleotides; synthetic molecules which can bind to two    components; etc. An example of use of a complexing agent is in    linking of an end of a nucleic acid fiber to a colloid particle or    linking of the two nucleic acid fibers to one another, for the    purpose of creating a junction.

SUMMARY OF THE INVENTION

The present invention makes use of the molecular recognition propertiesand self-assembly processes of nucleic acid sequences and othercomponents. These features are used to prepare fiber-based networks witha geometry defined by the type of interconnectivity between nucleotidechains of the fibers. The fibers may be made of nucleotide chains.Alternatively, the fibers may be made of substances other thannucleotide chains but comprising one or more nucleotide chains, and maybe connected to other network components through such chains. The fibersmay be wholly or partially a priori conductive, but are typicallychemically or physically modified so as to have electric or electronicfunctionality. The functionalized network may include conductors,switches, diodes, transistors, capacitors, resistors, etc.

The present invention provides, by a first of its aspects, an electronicnetwork with at least one network component, the network having ageometry defined by at least one fiber comprising one or more nucleotidechains.

The network component may be a conductor, e.g. a wire, or may be anelectronic component.

The fibers of the invention can form junctions in which one nucleotidechain segment of one fiber is bound to another nucleotide segment ofanother fiber by a sequence-specific interaction. Alternatively,junctions may be formed between nucleotide chains of different fibers,by a molecule, cluster of atoms or molecules or a particle which isbound to each of the nucleotide chains in the junction. Such a molecule,cluster or particle may be bound to the nucleotide chains throughlinkers bound to said molecule, cluster or particle.

The junction may also be formed by modified nucleotides, for example,modified such to allow covalent binding of at least one nucleotide ofone chain to a nucleotide of another chain. An example of suchmodification is the addition of a sulfur an amine residue, a carboxylgroup or an active ester. The chemical modification of a nucleotide mayalso allow a chain to bind a linker, to bind to a particle, to bind toan electronic component of the network, etc. The nucleotide chain mayalso be modified by binding thereto one member of a binding couple forbinding to another component comprising the other member of the bindingcouple. The binding couple consists of two molecules or moieties whichhave a specific affinity towards one another. Such binding couplesinclude biotin-avidin biotin-streptavidin, receptor-ligand, dig-antidig,antigen-antibody, sugar-lectin, nucleotide sequence-complementarysequence, and a nucleotide chain and a nucleotide binding protein.Typically, at least one nucleotide chain of the network has one or moresubstances or at least one cluster of atoms or molecules or particlebound thereto or complexed therewith such that at least one electric orelectronic component is formed with properties which are based onelectric charged transport characteristics of said one or moresubstances or at least one cluster of atoms or molecules or particle.

The electronic component in the network is electrically connected to atleast one fiber and is constructed either on a nucleic acid chain whichhas been chemically or physically modified by depositing one or moremolecules, clusters of atoms or molecules or particles thereon,rendering the chain to have electronic functionality, or beingconstructed by a molecule, cluster of atoms or molecules or a particlesituated at a junction between two or more nucleic acid chains ofdifferent fibers, rendering said junction to assume electronicfunctionality. The electronic functionality is based on electric chargedtransport characteristics of the one or more molecules, cluster of atomsor molecules, or particles. Electronic functionality may also at timesdepend on junction geometry.

The network is typically connected to interface components (electrodes)which serve as an input/output (I/O) interface between the network andthe external electronic circuitry or component.

According to one embodiment of the invention, the fibers have anucleotide skeleton which has been chemically or physically modified, bydepositing thereon or incorporating thereto one or more molecules,cluster of atoms or molecules or particles to render it electronicallyfunctional. The fibers, in addition to comprising one or more nucleotidechains, can also be substantially made (other than its nucleotidechains) of a variety of substances such as conducting or semi-conductingpolymers, other polymers which have been modified to render themelectrically or electronically functional (e.g. by depositing thereonmolecules, cluster of atoms or molecules or particles) or carbonnano-tubes.

Molecules, clusters of atoms or molecules, or particles, used for eitherchemical or physical modification of the fibers or within junctionsbetween fibers, may typically comprise or be made of one or more metalatoms, which impart charge transport characteristics onto said clusteror particle.

The skeleton of the network of the invention comprises acid fibers whichare assembled to form a network on the basis of their sequence specificinteraction with other fibers or specific binding to other components.In this manner networks with practically infinite variety of geometriescan be formed.

Substances or particles may be bound to the fibers based on theirgeneral (overall) chemical properties. This will typically yield asubstantially homogeneous deposition of the substance or particles alongthe fiber. A specific embodiment of such a homogeneous binding ofsubstances or particles is the formation of an electrical conductingwire on the nucleotide chain skeleton, e.g. where the conductingsubstance is metal, such as described below. Alternatively, substancesor particles may also be bound to the nucleotide chain in a sequence ordomain-specific manner in different portions of the fibers, namely in amanner which depends on the sequence of nucleotides at given portions ofthe nucleic acid chains.

Sequence or domain-specific deposition of substances at differentnucleotide chain portions may be performed in a number of differentways. For example, an oligonucleotide a priori bound to a certainelectronically functional substance or particle, may be made to bindonto a chain portion with a complementary sequence. Similarly, it ispossible also to bind different types of substances or particles, in asequence or domain-specific manner, also to a multi-stranded (e.g.double-stranded) nucleic acid fiber. This may be achieved, for example,by the use of a sequence-specific complexing agent which identifies andbinds to a specific site of a double-stranded nucleic acid chain. Thecomplexing agent may be an oligonucleotide, forming with adouble-stranded chain, a triple-stranded structure; a protein, e.g. aDNA-binding protein recognizing a specific double-stranded domain; andmany others.

By sequence or domain-specific binding, different types of substancesmay be bound to different portions of a given fiber or network offibers.

Particles, e.g. colloid particles or polymers, may be made to bind toone or more fibers, typically by the use of complexing agents orlinkers. Depositions of such particles may be utilized for the formationof electronic components, e.g. a single-electron transistor (SET).

The geometry of the network is defined by the fibers. In formation ofthe network the chemical complementary and molecular recognitionproperties may be utilized by employing a self-assembly process. Thefibers may be assembled to form the network by sequence-specificinteractions of the nucleotide chain with complementary sequences. Thismay be used for the formation of various junctions (e.g. T- orX-junctions, as exemplified in FIGS. 2A-2F and others). Specificmolecular recognition between nucleic acid chains and linkers orcomplexing agents (the linkers or complexing agents may beoligo-nucleotides or a variety of other molecules, macromolecules,supramolecular assemblies or particles) may be used to link the nucleicacid chains to interface components or to other network components, e.g.to particles situated at junctions between fibers.

The present invention also provides, as one of its aspects, a junctionbetween two or more conductors of a micro electronic network, whereineach of the conductors has an end segment proximal to the junctioncomprising a nucleotide chain bound to another chain within thejunction.

The invention also provides, by another of its aspects, a method formaking an electronic network, comprising:

(a) providing an arrangement comprising at least one electricallyconductive interface component;

(b) attaching a linker to the at least one interface component;

(c) contacting said arrangement with at least one fiber comprising atleast one nucleotide chain with a sequence capable of binding to thelinker, and permitting binding of said sequences to said linker,

(d) electrically or electronically functionalizing the at least onenucleotide chain by depositing thereon or complexing thereto at leastone substance or particles imparting electric or electronicfunctionality to the fibers.

It should be noted that the order of steps in the above method is notmaterial and may be changed. For example, step (c) may precede step (b),or the functionalizing step (d) may precede step (c).

The network may at times be formed at once by mixing all components in amedium and then allowing the components to self-assemble in a specificmanner, based on the pre-designed properties of the various components.Fibers may be designed to have specific nucleic acid sequences to allowtheir hybridization to complementary sequences in other fibers.Similarly, particles may be formed with specific, sequence ordomain-recognizing complexing agent bound thereto, to allow them to bindto nucleic acid chains in a sequence or domain-specific manner. Forexample, clusters or particles with three different oligonucleotidesbound thereto can be formed which will then bind to ends of threedifferent nucleotide chains, to form a junction between the three fiberscontaining a colloid particle. Similarly, in order to ensure binding ofthe network to the interface components in a specific manner, sequence-or domain-recognizing linkers may be immobilized on the interfacecomponents and brought into contact with the assembling network.

At other times the network may be formed in a sequential manner, e.g.first forming a first sub-network structure comprising part of thecomponents of the complete network and then the missing components (e.g.fibers, particles, etc.) may be sequentially added until the network iscompleted. Sub-network structures may, for example, be particles withseveral oligonucleotides connected thereto, branched-fiber structures,etc. The gradual assembly may also be based on the self-assemblyproperties of the nucleotide chains and of complexing agents and linkerswhich bind to the nucleotide chains in a sequence or domain-specificmanner. Furthermore, it is also possible, particularly in the case ofnetworks with a complex structure, to first prepare a plurality ofsub-network structures and then combine them for the formation of thecomplete network.

As will obviously be appreciated by the artisan, the formation of thenetwork may be aided by agitating the medium where the network isformed, by providing directional streams of fluid to orient the fibersto connect to a downstream network component at their other end, byapplying other biasing measures, etc. In forming wires of theinventions, electric potential between the two ends of the fiber onwhich the wire is formed, may enhance and provide directional depositionof a conducting substance, e.g. metal.

The nucleotide chains, which may be a priori single, double or multiplestranded, may be formed and replicated by a variety of methods includingrecombinant DNA methods involving production and reproduction of nucleicacid fibers by “engineered” cells, e.g. microorganisms; alternatively,the fibers may be produced synthetically, e.g. by synthesis of strandsand then combining them into larger fibers. The fibers may be formed bya variety of amplification techniques, e.g. polymerase chain reaction(PCR); etc.

Fibers constructed of nucleotide chains and other substances may beformed in a variety of ways. Typically, a non-nucleic acid fiber (e.g.made of a conducting polymer or being a carbon nano-tube) may be formedand covalently bound at both ends to specific nucleotide chains. Such afiber comprising a non-nucleotide fiber bound at its two ends to anucleotide chain may be used as such in constructing the network. Thefiber may be extended by binding to other stretches of nucleotides, bybinding to combined nucleotide-non-nucleotide fiber to obtain a longerfiber with intermitted nucleotide chains and non-nucleotide stretches,etc.

As will be appreciated, rather than binding a chain at an end of anon-nucleotide fiber, only a precursor may be bound and then the chainsynthesized in situ beginning with the precursor.

The non-nucleotide fiber stretches are typically a priori conducting orsemi-conducting, e.g. made of a conducting or semi-conducting polymer orco-polymer or a conducting nano-tube. In such cases no additionalfunctionalization of such non-nucleotide fiber stretches may be needed.However, the non-nucleotide fiber stretches may also be made a priorinon-conducting and can then be functionalized to become electrically orelectronically functional by doping or by chemical or physicaldeposition thereon of a variety of molecules, clusters or particles,e.g. those described above.

By an additional aspect the invention provides a junction between anelectronic component of an electronic network and an electricallyconducting interface component, comprising a nucleotide chain attachedto one of the electronic components or to the interface component andbound by a biomolecular interaction to a linker attached to the other ofthe two components.

By a still further aspect of the invention there is provided a networkcomponent as defined above. Examples of network components which may beformed in accordance with the invention are a switch, bipolartransistor, single-electron transistor, field effect transistor, diode,capacitor, resistor, conductor, light emitting diode, insulator,inductor.

While the above network components are useful within the network of theinvention, some may at times have utility in different applications.Their small size as compared to corresponding prior art components,allows them to be utilized in a variety of applications requiring asmall size or low energy consumption. A particular example of such acomponent is a wire.

A wire of the invention may be made to be very thin and may be used toadvantage in application requiring thin wires, for example, as a gate ina semi-conductor field effect transistor (FET) for a very fast gating ofsuch a transistor. The gating speed of a FET depends to a large extenton the width (referred to in the art at times as “length”) of the gatingwire in the FET. The wire in accordance with the invention may be madeto be about two orders of magnitudes smaller than the width of prior artgate wires of FETs, and accordingly, fast modulation, faster thanhitherto possible, can be obtained in a FET using a wire of theinvention. A FET comprising a wire of the invention as its gate is alsoan aspect of the invention.

The invention will now be illustrated by the following detaileddescription and subsequent examples, with occasional reference made tothe annexed drawings. It should be appreciated by the artisan, that theinvention is not limited to the specifically described embodiments butrather applies to the fill scope of the invention as defined above,namely, to the formation of a network, and components in the network, byemploying self-assembly properties of nucleic acid fibers and bydeposition or complexation of substances or particles onto or to thefibers using molecular recognition driven, self assembly process, torender the fibers or junctions between the fibers electronicallyfunctional.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A-1B show a matrix of interface components and linkers forbinding to the network of the invention on the one hand and connectingto external electronic circuitry or components on the other hand.

FIG. 1C illustrates an embodiment of immobilization of oligo-nucleotidelinkers onto the interface components.

FIGS. 2A-2F show six examples of junctions between nucleic acid chains.

FIGS. 3A-3B represent the manner of forming and functionalizing anucleic acid chain into a wire, with the conducting material beingsilver (the wire's skeleton consists of nucleotides).

FIG. 3C shows a possible current-voltage relationship of a wire formedas illustrated in FIGS. 3A-3B, which is dependent on the voltagescanning direction (presented by arrows on the curves).

FIGS. 4A-4B represent the manner of forming a wire on a nucleotideskeleton, where the electronic material is polyphenylene vinylene (PPV).

FIGS. 5A-5E show a number of examples of functionalized nucleotidechains consisting of a p/n junction (FIGS. 5A-5C), a graded p/n junction(FIG. 5D) and a bipolar n-p-n transistor (FIG. 5E).

FIG. 6 is a presentation of the manner of forming a single electrontransistor (SET) by one embodiment of the invention.

FIGS. 7A-7B are illustrations of a molecular switch in accordance withan embodiment of the invention.

FIG. 8A shows two examples of fibers in accordance with embodiments ofthe invention comprising both nucleotide chains and non-nucleotidestretches.

FIG. 8B is a schematic representation of a precursor fiber for thepreparation of a fiber in accordance with an embodiment of the inventionwhere the fiber's skeleton is essentially non-nucleic acid based, withnucleic acid chains forming only segments of the skeleton.

FIG. 9 illustrates the manner of forming two oligonucleotide chains atboth ends of a polythiophene fiber.

FIG. 10 illustrates the manner of attaching the derivatizedoligonucleotides to carboxylic groups formed at the end ofnon-nucleotide fibers.

FIG. 11 illustrates a manner of derivatizing terminal groups of carbonnano-tubes using amino derivatized oligonucleotides.

FIGS. 12A and 12B are illustrations of a semiconductor FET in accordancewith an embodiment of the invention, shown in a planar view (FIG. 12A)and in a cross-sectional view (FIG. 12B).

FIG. 13 shows the scheme for synthesizing an oligonucleotide, asdescribed in Example 1(A).

FIG. 14 shows a fluorescently labeled λ-DNA stretched between two goldelectrodes (dark strips) 16 μm apart.

FIGS. 15A and 15B show atomic force microscope (AFM) images of a silverwire on a DNA template connecting two gold electrodes 12 μm apart in afield size of 1.5 μm (FIG. 15A) and 0.5 μm (FIG. 15B).

FIG. 16A depicts a two terminal I-V curves of the silver wire preparedaccording to Example 9. The arrows indicate the voltage scan direction.The solid-line curves are repeated scans and demonstrate the stabilityof the samples. Note the asymmetry in the I-V curves corresponding tothe two scanning directions.

FIG. 16B shows the I-V curves of a different silver wire in which thesilver growth was more extensive than in FIG. 16A. The more extensivesilver growth resulted in a smaller current plateau, on the order of0.5V, and a lower resistance (13 MΩ vs. 30 MΩ in FIG. 16B). By drivinglarge currents through the wire, the plateau has been eliminated to givean ohmic behavior (dashed line), over the whole measurement range.

FIG. 17 shows an AFM image of the result of binding of gold colloids tobiotin-modified nucleotides.

DETAILED DESCRIPTION OF THE INVENTION

The formation of a network typically begins by providing a matrix ofinterface components, which provide the I/O interface between thenetwork and an external circuitry or external component. Illustration ofone embodiment of such an interface component matrix 100 is shown inFIGS. 1A-1B. Each of the interface components 102 is typically a metalelectrode having a network-connecting pad 104, and an external circuitryconnecting pad 106 linked by a connector portion 108.

As a preparatory step for the formation of the network, the connectingpads are treated to allow binding thereto of linkers 110, e.g.derivatized oligonucleotides, as shown in FIG. 1B. Examples of themanner of treatments are described below. (One embodiment of the mannerof immobilizing a linker oligonucleotide onto an interface component inseen in FIG. 1C and described below). Pre-prepared linkers 110 can thenbe attached to the pad 104, typically a different linker to each of thepads. The linkers 110, shown in a schematical manner in the enlargementat the right of the central portion 112 of the matrix, may beimmobilized onto pads 104, for example, by jet printing, e.g. in themanner described below in the Examples. In this manner, a differentlinker 110 may be attached to each of pads 104. Each of linkers 110 mayhave a selective binding ability to a different specific nucleic acidsequence, this feature being represented by the different shapes at theend of the linkers.

A network of functionalized fibers including wires (as herein definedand described, by way of example, below) and a variety of other networkcomponents formed on or at junctions between the fibers, can then becontacted with the matrix; the specific binding of nucleic acidsequences in the network's fibers to the linkers immobilized onto theinterface components results in a specific connectivity pattern of thenetwork to the interface components. Alternatively, nucleic acid chainsof the fiber may first be made to specifically bind to the linkers and,if required, the functionalization of the networks, i.e. the formationof electronically functional components, the formation of wires, etc.,may then be carried out in the formed nucleic acid-based network.Another alternative would be to first anchor several sub-networkstructures to the matrix of interface components and at a subsequentstep, or simultaneously, allow the sub-network to bind one another toform a complete network. Examples of sub-network structures includeseveral fibers connected together, particles or clusters of atoms ormolecules with several nucleic acid fibers attached thereto; etc. Hereagain, the fibers may be a priori electrically or electronicallyfunctional (wholly or partially) or the functionalization may be carriedout after formation of the network.

FIG. 1C is a schematic representation of one embodiment for immobilizingan oligonucleotide onto an interface component. Biotin molecules 120 and122 are bound, one to an oligonucleotide 124 and the other to a sulfurcontaining moiety 126. Biotin molecule 122 is immobilized onto interfacecomponent 128 through the sulfur containing moiety 126 and then whenstreptavidin molecules 130 are introduced into the medium, they yieldthe formation of a complexing agent 132, which is a supramolecularcomplex comprising biotin and streptavidin, which immobilizesoligonucleotide 124 onto interface component 128.

Oligonucleotide 124 may be modified, by a subsequent functionalizationstep, into a network component such as a conductor, a diode, atransistor, etc., in a manner to be exemplified below. Alternatively,they may serve as linkers for binding of a nucleotide-chain end segmentof a fiber.

Important components in the network of the invention are junctions whichserve a variety of functions. Several examples of junctions are shown inFIGS. 2A-2F. FIG. 2A depicts a junction 200, formed between twosingle-stranded nucleic acid fibers 202 and 204. The junction, in thisspecific example is formed by hybridization of a terminal end sequence206 in fiber 204 and a complementary sequence 208 in fiber 202. Thisjunction may serve as a T-type junction between nucleic acid fiberswhich can then be transformed into functionalized connecting junctionsby depositing an electrically conducting substance on fibers 202 and 204and junctions, e.g. in the manner to be described below.

Another type of junction 210 is shown in FIG. 2B. This junction isformed by a complexing agent 212 which may be a colloid particle, aprotein, another type of a macromolecule, a supramolecular structure,etc. In this case, the junction is formed between one single-strandedfiber 214 and another single-stranded fiber 216. However, it should beappreciated that such a junction may also be formed between twodouble-stranded fibers. The complexing agent may be bound to the fibersby a variety of means. The binding may be covalent or non-covalent.Examples of non-covalent binding are ionic interactions, hydrophobicinteractions, by means of Van der Waals forces, etc. The complexingagent may also be a complex molecular structure by itself, e.g. it maybe formed by two or more molecules or macromolecules with a bindingaffinity to one another of which at least one is bound to each of fibers216 and 214. Examples of such complex molecular structures are a largevariety of molecules which can bind to one another, such as for example:antibody-antigen, ligand-receptor, biotin-avidin, and many others.

A specific example of such a complex molecular structure is shown inFIG. 1C (above). Although this complex molecular structure, which is abiotin-streptavidin complex, is shown in its role as immobilizingoligonucleotide onto an electrode, the same complex molecular structuremay also be used for forming a junction between nucleic acid fibers(i.e. each fiber will be modified by binding a biotin and then the twoavidin moieties may be complexed by one streptavidin).

A further example of a junction 220 is shown in FIG. 2C. In this case, acomplexing agent 222 binds together two fibers 224 and 226. Thecomplexing agent and the manner of its interaction with nucleic acidfibers may be similar to complexing agent 212 in FIG. 2B.

Two other examples of junctions are shown in FIGS. 2D and 2E. Thesejunctions 230 and 240 are formed between three and four nucleic acidchains, respectively, each of which is double-stranded. Such junctionsmay be formed by hybridization or enzymatic synthesis, as describedbelow in the Examples.

Another type of junction 250 is shown in FIG. 2F. In this case, acomplexing agent 252, e.g. a colloid particle, links together aplurality of fibers, four 253-256 in this specific embodiment, each ofwhich is bound at its terminal to the complexing agent 252. The bindingof each of fibers 253-256 to particle 252 may be by means of directassociation, by the use of mediators such as specific binding proteins,in any of the manners described in connection with FIGS. 2B and 2C, etc.

In the following, some examples of fabrication of wires and electroniccomponents and functionalized networks of the invention will bedescribed. It should be understood that these are exemplary embodimentsonly and various modifications of the described embodiment are possible,all being within the scope of the invention as defined herein.

Reference is now being made to FIGS. 3A-3B, showing the manner offormation of a wire in accordance with an embodiment of the inventionwhich in this specific case is a wire formed on a nucleotide skeleton.As illustrated in FIG. 3A, the wire here is formed between twoelectrodes 300, typically made of, or coated by metals such as gold,platinum, silver, etc. Electrodes 300, which may be first treated in amanner to facilitate subsequent binding of the linker, are wettedseparately with a solution containing either linker molecules 302 or304, each consisting of a single-stranded oligonucleotide (“Oligo A” and“Oligo B”, respectively), derivatized by a disulfide group. When theselinkers are deposited on electrodes 300, under appropriate conditions,the disulfide group bind to the electrodes 300, to form linkers 306 and308, respectively (step (a)). Electrodes 300 are then wetted with anucleotide chain solution, e.g. a DNA double-stranded fiber, 310, havingsticky ends, complementary to the sequences of the oligonucleotides inlinkers 306 and 308. Electrodes 300 are spaced from one another at adistance about equal to the length of the nucleic acid fiber 310,whereby each end of nucleic acid fiber 310 binds to its complementaryoligonucleotide in one of linkers 306 and 308 to form a bridge 312between the two electrodes 300 (step (b)). By controlling theconcentration of oligonucleotide 310 in the medium, the number of suchbridges formed between the electrodes can be controlled. Followinghybridization the binding of the linkers to the nucleic acid fibers maybe strengthened by covalent binding of the two to one another byligation of the nicks.

At times, particularly where fiber 310 is long and thus it is notpractical to ensure its hybridization at both ends merely by relying ondiffusion, the strand 310 may be made to connect to one electrode andthen, by a directional stream of fluid from the first electrode to thesecond, the nucleic acid fiber is made to extend so that its end reachesthe second electrode.

It is also clear that in order to avoid folding of the nucleic acidfibers and to ensure proper binding, appropriate solutions may need tobe at times selected.

The functionalization step of the fiber, for the purpose of constructinga metal wire, begins, according to the specifically illustratedembodiment as shown in FIG. 3B, by an ion exchange step involvingexposure of the fiber to a solution comprising silver ions (Ag⁺) underalkaline conditions, whereby the silver ions replace the sodium ions orother ions normally associated with the nucleotide chain and complexwith the negatively charged fibers (step (c)). This gives rise to anucleic acid fiber 314 loaded with silver ions 316. It should be noted,that rather than silver ions, a wide variety of other metal ions can beused, including for example, cobalt, copper, nickel, iron, gold, etc.Furthermore, metal aggregates, complexes or clusters, e.g. colloidalgold, colloidal silver, etc., may also be deposited on the nucleic acidfiber via a variety of different interactions. The ion-exchange steptypically involves rinsing of the fibers with deionized water, and thensoaking them in a solution of the metal ions or metal aggregates.

At a next step (step (d)), the fiber is exposed to a reducing agent,e.g. hydroquinone, which yields a reduction of the metal ions in situinto metallic silver. The metallic deposit, e.g. metallic silver, isformed at a number of nucleation sites 318. After rinsing with deionizedwater, the fibers with nucleation sites 318 are contacted with a reagentsolution comprising metal ions and a reducing agent, e.g. hydroquinone,under acidic conditions. Under these conditions, the ions are convertedto metallic metal only at the nucleation site and consequently thenucleation centers grow to form a conductive wire 320 (step (e)).

It should be noted that the silver nucleation centers can also beenhanced by chemical deposition of gold or other metals. Similarly, goldnucleation centers may be enhenced by deposition of gold, silver as wellas other metals.

The so formed wire 320 may be subjected to a variety of post fabricationtreatments, which may include, for example, thermal treatment intendedto increase the wire's thickness and homogeneity; passivation treatmentfor the purpose of forming an electrically insulating layer around thewire, e.g. by exposure to alkane thiol; electrochemical or photochemicalgrowth of the wire by polymers on the wires; etc.

FIG. 3C illustrates a typical current-voltage relationship of a wireformed by the procedure illustrated in FIGS. 3A-3B. As can be seen, thecurves are non linear and are asymmetric with respect to zero bias. Theshapes of the curves depend on the scan direction as indicated by thearrows in FIG. 3C. Approaching zero voltage from a large positive ornegative bias, the current vanishes almost linearly with the voltage. Azero current plateau then develops with very large differentialresistance. At a higher bias, the wire turns conductive again with adifferent channel resistance. This history-dependent current-voltagerelationship, may render the wire as a logic or memory component.

As may be appreciated, in a similar manner, mutatis mutandis, fibers ofthe kind shown below in FIG. 8A may be prepared. The requiredfunctionalization step may then only be needed with respect to theterminal or intermediate nucleotide chains.

Reference is now being made to FIGS. 4A-4B, showing the manner offormation of a wire in accordance with another embodiment of theinvention. Here again the wire is formed on a nucleotide skeleton. Aspointed out above, with reference to the embodiment of FIGS. 3A-3B, asimilar procedure, mutatis mutandis may be followed with respect to afiber of the kind shown in FIG. 8A. In the embodiment shown in FIG. 4A,in distinction from that of FIG. 3A, rather than metal, the depositedmaterial is PPV (poly-phenylene vinylene). Electrodes 400, may be thesame as electrodes 300 shown in FIG. 3A. The first two steps of themethod (steps (a) and (b)), are substantially identical to thecorresponding steps in FIG. 3A (identical components have been given areference numeral with the same last two digits as the correspondingcomponents in FIG. 3A: e.g. 402 is the same as 302, 404 as 304, etc.).The formed bridge 412 may be strengthened, similarly as above, bycovalent binding of fiber 410 to linkers 406 and 408 to yield a completefiber 414 connecting the two electrodes (step (c)).

As shown in FIG. 4B, a solution comprising pre-PPV⁽²⁶⁾ molecules 416 isthen contacted with fiber 414 and by the virtue of being positivelycharged, pre-PPV 414 becomes complexed with the negatively charged DNAbridge 414 (step (d)). At a next step, the sample is rinsed, dried andfinally heated in a vacuum, e.g. to a temperature of about 300° C., forabout 6 hours, which leads to the release of tetrahydrothiophene groupsand hydrochloric acid from each repeat unit, yielding a luminescent PPVcomponent (step (e)).

In order to convert the PPV into a conductor, this polymer is doped withagents which either cause electron deficiency (holes) or give rise toextra electrons. Doping may be performed by many known methods e.g.exposure to H₂SO₄ vapor, addition of halo-acid vapor (e.g. HCl, HBr), bythe use of dodecyl benzene sulfonic acid, by the use of camphor sulfonicacid, or by other means. The extent of doping determines theconductivity of the wire.

Many other polymers may be used instead or in addition to PPV inaccordance with the invention. This includes a variety of polymers withpositively charged side groups as well as polymers with positivelycharged groups in the backbone or polymers with recognition groupscapable of binding to nucleic acid fibers. Another example of a polymeris polyaniline (PANI). These polymers include such which have either anelectron deficiency (p-type polymers) or have electron surplus, (n-typepolymers). In addition in a similar manner, mutatis mutandis, othertypes of conducting substances (n-type or p-type substances) may bebound to the fiber.

By the use of oligonucleotides bound to various substances which canimpart electronic functionality, the properties of the electroniccomponents assembled on a nucleic acid fiber can be preciselycontrolled. For example, two oligonucleotides, of which one has asequence to allow hybridization to a specific portion of the fiber, andis bound to a p-type substance, and another has a sequence allowinghybridization to an adjacent portion of the fiber, bound to an n-typesubstance, (a polymer with an electron surplus) are made to bind to thefiber, and in this manner, an n/p junction can be formed, e.g. servingas a diode. Another example may be the formation of a p-n-p or an n-p-ntype, bipolar transistor.

An example of some functional components which may be formed on anucleotide chain are shown in FIGS. 5A-5E. In FIG. 5A, a p/n junction isformed by a p-type substance 510 bound to one oligonucleotide 512, whichis a poly C in this specific example, and an n-type substance 514 boundto another oligonucleotide sequence 516, a poly A in this specificexample. The oligonucleotides bind to complementary sequences 518 and520, respectively, on the nucleotide fiber 522 and after coupling, a p/njunction is formed. In FIG. 5A, the p/n junction is formed on asingle-stranded segment of fiber 522. Similarly, such a junction mayalso be formed on a double-stranded fiber 524 (see FIG. 5B), e.g. byfirst removing a portion of one strand, e.g. by enzymatic digestion toexpose adjacent segments 526 and 528 and then hybridization with thecomplementary p-type and n-type substance-carrying oligonucleotides 530and 532, respectively.

The remaining portion of the fiber, may, for example, be treated in amanner to fabricate a wire, such as that described above with referenceto FIGS. 3A-3B or 4A-4B, and accordingly a diode (a p/n junction) 534 isformed with conducting wires (C) 536 and 538 flanking the two ends ofthe diode (FIG. 5C). In order to ensure that the conductor substance isnot deposited on the p-n junction portion, the materials constitutingthe junction may first be coupled and only then the remaining portion ofthe fiber may be treated in a manner described above to form aconducting wire.

FIG. 5D is a schematic representation of another structure which in thiscase consists of two conducting wires (C) formed on two peripheral fiberportions 540 and 542 which flank a portion of the fiber which wastransformed into a graded p/n junction 544. This exemplified junctionconsists of portions which are heavily doped 546 and 548 (ppp and nnn)portions which are moderately doped 550 and 552 (pp and nn) and portionswhich are only slightly doped 554 and 556 (p and n).

Another functionalized structure is shown in FIG. 5E. This structure isa junction which has a T-type branch point 560 and by converting theportion of the junction into an n-p-n bipolar junction 562 asillustrated (or a p-n-p junction) and then converting the remainingportions of the fibers 564, 566 and 568 into wires, a bipolar transistoris formed.

Specific depositions of various substances can also be achieved by meansother than hybridization. For example, various molecules, e.g. proteins,which are capable of recognizing specific domains, even without the needto “open” the double or multi-stranded nucleotide chain, may be used forthis purpose.

p-n junctions may also be obtained in accordance with the invention infibers of the kind illustrated in FIG. 8A, which consists of nucleotidechains attached to non-nucleotide fiber stretches made of asemi-conducting polymer. Where the semi-conducting polymer is p-type, ann-type polymer may be deposited on the nucleotide chain segment adjacentthe semiconductor fiber segment in an analogous manner to that shown inFIGS. 5A-5E. Similarly, a p-n junction may be found by depositing ap-type polymer on a nucleotide chain segment adjacent an n-typesemiconductor fiber sequence.

FIG. 6 shows a manner of construction of a single electron transistor(SET). A particle, 600 is made to bind with three differentoligonucleotides 602, 604 and 606. One of the oligonucleotides is boundto particle 600 through a large non-conducting complexing agent 608,e.g. a protein or a supramolecular structure, the purpose of which willbe explained further below. In an array of three electrodes 610, eachelectrode is bound to one of fibers 612, 614, and 616 (which may be anucleotide fiber, a fiber of the kind illustrated in FIG. 8A andothers), each of which has a different sticky end, complementary to asequence in one of the oligonucleotides 602, 604 and 606. Theoligonucleotides-dressed particle is contacted with the electrode arrayand by providing conditions for hybridization, a structure 620,consisting of electrodes 610 bound to particle 600 through threebridges, each of which consists of one of fibers 612, 614 and 616 andone of oligonucleotides 602, 604 and 606, respectively, is formed.Fibers 612, 614 and 616 may be made to covalently bind tooligonucleotides 602, 604 and 606, respectively, to form integral fibers622, 624 and 626.

The particle is subjected to passivation treatment, e.g. by means ofexposure to alkane thiol, octadecyl thiol, dodecyl thiol, etc., to forman insulating layer 630 to isolate the colloid particle from thesurrounding medium and avoid metal deposition on the colloid particle ina subsequent step. Fibers 622, 624 and 626 are then formed into wires,e.g. in the manner described above, whereby a SET is formed.

In the SET, wire 622 serves as a gate and for its proper function, ahigh resistance between it and the particle 600 is preferred, whichpurpose is achieved by complexing agent 608. Under normal circumstances,particle 600 resists a current flow, but when the potential at the gateis changed, the electrostatic field formed reduces the activation energyrequired to charge or discharge the colloid particle whereby current canflow between wires 624 and 626.

As will be appreciated, the manner of construction of the SET describedherein is but an example. One alternative method is first formation of aparticle with fibers attached thereto and then causing the fibers tobind to the electrodes, e.g. through oligonucleotide linkers. As will beclear to the artisan, there are other possible alternatives allowing toconstruct a SET in accordance with the invention.

Reference is now being made to FIGS. 7A-7B, illustrating a molecularswitch which is based on a reversible photo transformation. A molecularfragment, such as bis thiophene derivatives of hexafluorocyclopentene ormaleimide, (FIGS. 7A and 7B, respectively), are bound to the networks.Polymer groups (P1 and P2 (which may be the same or different)) that maycontain recognition groups which may be sequence selective or nonsequence selective, are attached to both thiophene moieties via covalentor non covalent interaction to form a disrupted conjugated polymer. Thepolymers P1 and P2 are each connected to a different fiber (P1 and P2,respectively—not shown). Upon exposure to light with an appropriatewavelength (λ), photocyclization of the thiophenes with a double bond ofthe hexafluorocyclopentene or maleimide occurs, thus forming aconjugated polymeric wire electrically linking P1 and P2. Photoexcitation of the cyclized switch results in the retrocyclizationprocess and redisrupts the conjugation along the polymer.

The switching light signal may be provided from an external lightsource, or may be provided internally by any internal light source.

FIG. 8A illustrates schematically other embodiments of fibers inaccordance with the invention: whereas the fibers shown above in FIGS.3A-3B and 4A-4B, had a nucleotide skeleton, the fibers shown in FIG. 8Ahave a skeleton which is a composite structure consisting of bothnucleotide segments and non-nucleotide segments. FIG. 8A shows twoembodiments of fibers, fiber 700 and fiber 710. Fiber 700 has, as amajor portion, a non-nucleotide fiber stretch 702 whose terminals arelinked to two nucleotide chains 704 and 706. Non-nucleotide fiberstretch 702 may be a polymer, conducting, semi-conducting ornon-conducting, or may be a nano-tube, e.g. a carbon-based nano-tube.

Fiber 710 consists of several non-nucleotide fiber stretches 712, 714,716, connected by nucleotide chains 718 and 720 and flanked by twoterminal nucleotide chain sequences 722 and 724. In such compositefibers, the oligonucleotide chains serve as recognition groups forbinding to oligonucleotide chains of other fibers. Preferably, thenon-nucleotide fiber stretches (702, of fiber 700 and 712, 714 and 716of fiber 710) are made of a conducting or a semi-conducting material.The use of such non-nucleotide segments facilitates the construction ofa variety of electronic components. Such substances may be of amolecular, macromolecular or non-molecular (heterogeneous) character andmay be made of oligomers and polymers of thiophenes, pyrroles, anylines,acetylenes, phenylenes, metal complexes (such as axially interconnectedporphyrins, platinum complexes, etc.) and nano-tubes, e.g. carbon-basednano-tubes.

As illustrated schematically in FIG. 8B, such non-nucleotide fiberstretches may be selectively derivatized with active groups (R¹ and R²)at their terminal sites. R¹ and R², may be the same or different and mayrepresent —NH₂, —CO₂H, —CO₂R—Br—B(OH)₂, and many others.

Oligonucleotides bearing the complementary moieties may be covalentlycoupled to these terminal active groups. For example, a polythiophenecan be prepared having two carboxylic groups at its two ends, as shownin FIG. 9. To these carboxylic groups, amino derivatizedoligonucleotides may be attached using different methods, one as shownin FIG. 9 by the use of EDC by the formation of active esters on thecarboxylic groups in a manner shown in FIG. 10, where “R” represents theconductive wire.

A similar approach may be applied for the selected derivatization ofterminal groups of carbon nano-tubes using amino derivatizedoligonucleotides. Carbon nano-tubes may have carboxylic groups at theirtwo terminal ends (Wong et al., Nature, 394:52, 1998). To these ends,amino derivatized oligonucleotides may be attached via active estercoupling, as can be seen in FIG. 11.

A variety of other coupling methods may be applied for the connection ofoligonucletoides to a fiber such as the use of metal ion-ligandinteraction, the use of metal-metal complex, metal ion catalyzed heterocoupling methods, and others.

FIGS. 12A-12B are schematic illustrations of a FET in accordance withthe invention. The FET 800 comprises source electrode 802, a drainelectrode 804, situated at two ends of a semiconductor matrix 806. Gatewire 808, connected to gate electrode 810, is situated in a recess 812,within semiconductor matrix 806. The gate length in a semiconductor FETdetermines, to a large extent, the maximal frequency at which the FETcan operate. Shorter gates minimize the electron flight time under thegate and hence facilitate higher operation frequencies. Since FETdimensions, apart from the gate, are not critical, the gate parametersset the bottle neck for mass production of faster FETS. The FET inaccordance with the invention provides a solution to this problem. TheFET, apart from the gate, may be fabricated by conventional lithographyand semiconductor processes and techniques, and then the gate may beformed by stretching a nucleic acid fiber between electrodes and thenthe fiber may be metalized as outlined above. In this manner sub-0.1micrometer gates can easily be formed allowing inexpensive massproduction of faster FETS.

The invention will now be illustrated further in the following Examples.

EXAMPLES Example 1 Preparation of Linkers

(a) Disulfide Based Linkers:

Controlled pore glass (CPG) derivatized with a disulfide group is usedfor the synthesis (starting from its 3′ side) of an oligonucleotidehaving a free 5′ site. The oligonucleotide is prepared using aconventional DNA synthesizer (see scheme in FIG. 13).

(b) Thiol-Based Linkers:

Linkers are being prepared according to (a) above and the disulfide bondis cleaved to obtain a free thiol.

(c) Biotin-Streptavidin Complex Based Linkers:

Biotin moiety is attached to an oligonucleotide having a specificsequence, as known per se. The biotin-oligonucleotide is coupled via astreptavidin molecule to another molecule containing a biotin moiety atone side (see also FIG. 1C) and a thiol or disulfide group on the otherside.

(d) Repressor Based Linkers:

A nucleic acid binding protein, such as the lac repressor, is covalentlyattached to a thiol group. A DNA sequence is synthesized having stickyends and containing the target sequence to which the repressor binds.The DNA sequence is coupled to the repressor through the targetsequence.

(e) Thiophosphate Based Linkers:

The construction (starting from its 3′ side) of an oligonucleotidesequence is carried out using a conventional DNA synthesizer whereinthiophosphates containing nucleotides are used instead of phosphatecontaining nucleotides.

(f) Artificial Site Specific Based Linkers:

A synthetic site-specific moiety such as, for example Rh(Phen)₂Phi,known to bind 5′-pyr-pyp-pur-3 sequence⁽²⁶⁾ (pyr=pyrimidine,pur=purine), is covalently coupled to a thiol group.

Example 2 Attachment of the Linker to an Electrode

(a) Micropipette Wetting:

Electrodes are exposed to solutions of the appropriate linkers, forexample, by employing pipettes or micropipettes or by any liquiddispensers. Such liquid dispensers may be fixed onto a manipulator thatmay be computer controlled. Different types of linkers can be depositedon each electrode. Additionally, different types of linkers can bedeposited simultaneously or sequentially on different electrodes.

(b) Jet Printing:

Ink-jet like printing techniques are used for the selective exposure ofdifferent electrodes to different linkers. By utilizing such atechnique, it is possible to attain high precision, resolution and toincrease rates of production, facilitating large scale production.

(c) Ab-Initio Electrode-Linker Synthesis:

(c1) Using Selective Masking Techniques:

The well developed technology used for synthesizing DNA sequences may beharnessed for the ab-initio preparation of a complex electrode-linkerarray. For example: an inert substrate composed of a set of electrodesis partially coated with an inert coating yielding two types ofelectrodes: coated electrodes (A) and uncoated electrodes (B). Thesubstrate is exposed to a solution of a thiol linked to a nucleic acidsequence serving as a starting point for DNA synthesis. Due to the inertcoating, only the uncoated B electrodes react with the thiol. Usingstandard DNA synthesizing techniques, a pre-defined sequence is producedon the B electrodes. The substrate is then rinsed and the maskedelectrodes are uncovered followed by the selective coating of Belectrode. This procedure allows the production of two types ofelectrodes differing one from the other by the type of linkers boundthereto. The same technique with somewhat more complex steps (severalsteps of masking and unmasking) allows the fabrication of varioussubstrates having many different electrodes with different linkers boundthereto.

(c2) Using Photodeprotection Techniques:

This approach involves the utilization of photolabile groups for theprotection of the start point of DNA synthesis. Inactivated start pointgroups are unable to react with nucleotides. Using selective irradiationby means of a mask and/or a light conductor and/or any other addressablelight source, the activation of different selected electrodes isachieved by the photoremoval of protecting groups from selectedelectrodes.

(c3) Using Blockers:

Using the masking technique ((c1) above) a set of electrodes is preparedfor oligonucleotide synthesis. Once a DNA sequence is completed on oneset of electrodes, a terminating group is attached to theoligonucleotide ensuring their inertness. Other sequences can be furthersynthesized on different electrodes that are prepared according to theprevious step but become active according in this step. It should benoted that the set of linkers constructed in the previous step is notaffected due to the attached blockers to their end points.

(c4) Electrode Printing:

Linkers are attached to conducting beads such as gold colloids. Thecolloids are then dispersed in a controllable manner to form conductingmetal pads with linkers attached thereto. Dispensing may be achieved bythe different techniques outlined above or by any conventionaltechnique.

The above techniques may be used alone or in any combination with othertechniques.

Example 3 Construction of Networks—Production of Junctions

(a) Production of a Branched Sequence:

A stable four-arm branched DNA junction is constructed using for examplethe following sequences:

               C-G                G-C                C-G               A-T                A-T                T-A               C-G                C-G G C A C G A G T   T G A T A C C GC G T G C T C A   A C T A T G G C                C-G                C-G               G-C                A-T                A-T               T-A                G-C                C-G

Careful planning of the sequences allows the fabrication of complexjunctions according to a desired design. This branch sequence may beattached to double-stranded fibers using methods known per se.

(b) Creating a Branch by Enzymatic Reactions:

The protein recA from E. coli bacteria catalyzes the recombination andconstruction of a base-paired hybrid to joining two DNA molecules. Itcan join, in a specific way, a single-stranded DNA with adouble-stranded DNA provided that homology exists between thesingle-stranded and the double-stranded DNA. DNA-binding proteins canextend single-stranded DNA and facilitate DNA annealing by randomcollisions. It is also possible to achieve base-pair specific contactsbetween two separate duplexes to form a four-stranded structure that isaligned through chemical moieties exposed in the grooves of the twohelices. Similarly, the recA protein can induce specific contactsbetween a single-stranded and a double-stranded DNA, through recognitionof the complementary sequence from the “outside” without the need toopen the double strands and expose the single-strand sequence. There isalso the possibility to recombine three-stranded and four-stranded DNAhelices. Four DNA strands can also undergo “switch pairing” at a joiningpoint to form a crossed-strand junction (called Holiday structure).There is then the possibility to create the so called heteroduplexeswhich are regions on recombinant DNA molecules where the two strands arenot exactly complementary. The branching joint, however, can migrate toits equilibrium point of complementary base paring. Fully recombinantduplexes are formed by allowing steric rearrangements. The utilizationof RecA protein for making the Holliday structures in vitro is wellestablished (see, for example B. Alberts, et al., Molecular Biology ofthe Cell, 3rd Edition. Garland Publishing Inc., New York, 1994). Anotherenzyme. RecBC from E. coli bacteria has both unwinding and nucleaseactivities and can therefore catalyze the exposure of single-strandedDNA with a free end, allowing the RecA protein to start the pairingreaction. Important for the step-by-step build-up of the network, is thefact that RecBC initiates unwinding only on DNA containing a free duplexend. It then navigates along the DNA, from the free end, unwinding andrewinding DNA as it goes. Because it unwinds the DNA faster thanrewinding it, “bubbles” or loops of single-stranded regions are createdin the duplex DNA. RecA protein can then bind to a cut, made by theRecBC in a specific sequence, 5′-GCTGGTGG-3′, in one of the singlestrands and initiates DNA strand exchange with another DNA. The specificsequence of the cut can be pre-designed by artificial recombinant DNAsynthesis (see B. Alberts et al, supra and L. P. Adams et al., TheBiochemistry of the Nucleic Acids, 11th Edition, Chapman & Hale, 1992).

(c) Utilizing Nucleic Acid-Binding Proteins:

Two or more specific DNA binding proteins are allowed to interact withtwo or more DNA strands. Coupling of such binding proteins enables theformation of a junction between the different DNA strands.

Example 4 Connection of Network to Substrate

Anchoring the network to the substrate may be realized using various DNAbinding proteins. For example, repressors from bacteria (e.g.lac-repressor or λ-repressor) which can bind to both the substrate (suchas a plastic substrate) and to the DNA thus joining the two. Suchbinding stabilizes the network without necessarily taking part in theelectrical functionality.

Example 5 Preparation of an Integrated Circuit

The integrated circuit (IC) is composed of a substrate such as silicon,derivatized silicon, silica, derivatized silica, organic polymer or anyother substance capable of acting as a support for the fabrication ormechanical fixation or stabilization of the network. The substrate mayserve an electrical function.

A typical example for IC preparation is described in the following:

Example 6 Passivation of a Glass Substrate

A glass substrate is immersed in fuming nitric acid (100% HNO₃) for 10min, rinsed in deionized (DI) water, then immersed in 1 N NaOH solutionfor an additional 10 min and rinsed in DI water. The cleaned glass isdried thoroughly, then immersed for c.a. 12 hrs in a solution of analkyl tricholorosilane (octyl trichlorosilane, t-butyl trichlorosilaneetc.) in tetrachloroethane (1:5 v/v). The glass plate is then rinsedcarefully several times with tetrachloroethane and isopropanol, thendried thoroughly.

Example 7 Electrode Fabrication

Electrodes are fabricated according to one of the following routes: (i)Standard photo, electron, or x-ray lithography on the substrate andsubsequent deposition of conductive substance (e.g. metal).Alternatively, the conductive substance may be deposited first andpatterned next. (ii) Electrode assembly onto the surface: Patterning ofthe glass surface using polyelectrolytes such as polyetheyleneimine,polyalcoholes, polyacids, polypyridines etc. or other ligating agentssuch as a thiol monolayer (fabricated from organic compounds containingthiol and silane moieties at opposite sites on the molecular skeleton)followed by the fixation of electrically conducting components such asGold colloids enabling the assembly of conducting electrodes onto thesubstrate.

Example 8 Electrical Functionalization of the Nucleic Acid BasedNetworks—Metal Based Conductive Wires

(i) The relevant part of the network is exposed to a solution containingthe appropriate metal ion, thus, ion exchange occurs at the phosphategroups of the DNA skeleton exposed to the solution. Intercalation ofions inside the DNA may also take place under certain conditions

(ii) The ion exchanged DNA complex is then reduced by a reducing agentsuch as hydroquinone.

Cycles (i) and (ii) can be repeated in a sequential order until aconducting wire is achieved. Alternatively, the formation of conductingmetal wire includes the following steps as stand-alone processes or inconjunction with steps (i) and (ii) or combined with one or more of thefollowing techniques.

(iii) The relevant part of the ion-exchanged network is exposed to ametastable mixture of the reducing agent and the metal ion. Reductiontakes place only at the surface of the metal clusters formed by steps(i) and (ii) thus, the gap between the metal clusters is bridged by themetal deposition process.

(iv) The ion exchanged DNA or the partially treated DNA network isexposed to electrochemical process, transforming the ions loaded on theDNA polyelectrolyte into a metallic conductor. In addition,electrochemical processes along the DNA molecule promote the vectorialgrowth of the metal wire along it.

(v) Photochemical deposition of the metal from its corresponding ionsfor the formation of the metallic wire.

(vi) Clusters or colloids are adsorbed onto the DNA network usingsequence selective components, for example, specific sequences which arecapable of binding to specific sites on the DNA, ornon-sequence-specific binding agents, e.g. polyelectrolytes undergoingelectrostatic interactions with the DNA. These Clusters and/or colloidsserve as catalysts for processes (iii)-(v) above.

(vii) Defects in granular wires fabricated by one or more of the abovetechniques may be annealed using diverse methods such as thermalannealing processes, electrodeposition, etc.

An example of the fabrication of a silver-functionalized network is asfollows:

(i) A DNA network fixed on a substrate is exposed to a basic solution ofsilver ions (pH=10.5, NH₄OH, 0.1 M AgNO₃). After the DNA polyelectrolyteis exchanged by the silver ions, the substrate is rinsed carefully withdeionized water (DI) and dried.

(ii) The silver loaded DNA network fixed on a substrate is exposed to abasic solution of hydroquinone (0.05 M), pH=5 as a reducing agent. Steps(i) and (ii) are repeated sequentially until an electrically conductingwire is formed.

(a) Complementary Processes:

Step (iii) is performed after one or more (i)+(ii) cycles.

(iii) The DNA network loaded with silver metal clusters (after cycles(i) and (ii) have been performed) and after final rinsing with DI wateris exposed to an acidic solution of hydroquinone (citrate buffer,pH=3.5, 0.05 M hydroquinone) and AgNO₃ (0.1 M). Cycle (iii) isterminated when the wire width attains the desired dimension. Theprocess can be made light sensitive and thus can also be controlled bythe illumination conditions.

(b) Electrochemical Deposition for Improved Process:

(iv) In order to improve the aspect ratio of the metallic conductor, anelectrochemical process is performed. For that purpose, pre-treatmentwith an alkane thiol is performed prior to the (i)+(ii) processes. Thisensures the inertness of the metal electrodes against electrochemicalmetal deposition. After one or more of the (i)+(ii) cycles, theelectrodes connected through the DNA covered metal wire are connected toa current and bias controlled electrical source and the relevant part ofthe DNA network is exposed to a solution of the metal ion (differentconcentrations according to a specific protocol). The gaps between theconducting domains are filled via electrochemical metallic deposition.

(c) Photochemical Deposition for an Improved Process:

(v) In order to improve the aspect ratio of the metallic conductor, aphotochemical process is performed in a similar manner to theelectrochemical process outlined above but using photochemical reactionsas driving processes. For example, metalization of a DNA network may beobtained using an electron donor (triethanolamine, oxalic acid, DTTetc.), a photosensitizer (Ru-polypyridine complexes, xanthene dyessemiconductor particles such as TiO₂, CdS etc.), an electron relay suchas different bi-pyridinium salts and the relevant metal ion or metalcomplex. The photosensitizer transduces the absorbed light energy into athermodynamic potential through electron transfer processes involvingthe electron donor and electron acceptor in any of the possiblesequences. The reduced electron acceptor acts as an electron relay andcharges the metal clusters/colloids with electrons. The chargedclusters/colloids act as catalysts for the reduction of the metal ionsthus inducing the growth of the metal conductor.

(d) Gold Clusters, Gold-Containing Molecules and/or Colloids asNucleation Centers:

(vi) Instead of performing the first (i)+(ii) cycles, the relevant partof the DNA network is exposed to a solution of gold clusters, moleculesor particles pre-coated (partially) with cationic thiols (such aspyridinium alkane thiol). The gold particles are being adsorbed to theDNA skeleton by ion pairing and the growth of the wire is attained usingone or more of the above techniques.

(e) Curing Processes:

(vii) Defects in a granular wire obtained by one or a combination of theabove techniques are annealed using diverse processes such as thermalannealing processes (hydrogen atmosphere (10% H₂ in N₂), 300 C. overseveral hours).

Example 9 Connecting Two Electrodes by a Conductive Wire Formed on a DNATemplate, and Properties of the Wire

(a) Wire Preparation:

FIGS. 3A-3B outline the DNA templated assembly of a metal wire. A glasscoverslip was first passivated against spurious DNA binding.Subsequently, two parallel gold electrodes were deposited on thecoverslip using standard microelectronic techniques. One gold electrodewas then wetted with a micron size droplet of an aqueous solutioncontaining a 12-base, specific sequence oligonucleotide, derivatizedwith a disulfide group attached to its 3′ side. Similarly, the secondelectrode was marked with a different oligonucleotide sequence. Afterrinsing, the sample was covered by a solution of about 16 μm long λ-DNA,having two 12-base sticky ends that were complementary to theoligonucleotides attached to the gold electrodes. A flow normal to theelectrodes was induced to stretch the DNA, allowing its hybridizationwith the two distance surface-bound oligonucleotides. Stretching the DNAbetween two electrodes could also be carried out in reverse order, wherehybridization and ligation of the disulfide derivatized oligonucleotidesto the long DNA molecule was performed prior to its application to thesample. Both methods work equally well. FIG. 14 depicts afluorescently-labeled λ-DNA bridging two gold electrodes. By observingthe curving of the DNA molecule under perpendicular flow it wasdemonstrated that it was attached solely to the electrodes. Samplepreparation was completed by removal of the solutions.

Two-terminal measurements performed on these samples prove that thestretched DNA molecule was practically an insulator with a resistancehigher than 10¹³ Ω. The insulating nature of the DNA was in accordancewith previous spectroscopic electron-transfer rate measurements⁽¹⁸⁾. Toinstill electrical functionality, silver metal was vectorially depositedalong the DNA molecule. The three-step chemical deposition process wasbased on selective localization of silver ions along the DNA throughAg⁺/Na⁺ ion-exchange⁽¹⁹⁾ and formation of complexes between the silverand the DNA bases⁽¹⁹⁻²²⁾. The Ag⁺/Na⁺ ion-exchange was monitored byfollowing the quenching of the fluorescence signal of the labeled DNA.The process was terminated when fill quenching was achieved. Afterrinsing, the silver ion-exchanged—DNA complex was reduced using a basichydroquinone solution. This step resulted in the formation of namometersize metallic silver aggregates bound to the DNA skeleton. These silveraggregates serve as spatially localized nucleation sites for subsequentgrowth of the wire. The ion-exchange process was highly selective andrestricted to the DNA template only. The silver aggregates bound to theDNA, were further “developed”, much as in the standard photographicprocedure, using an acidic mixture of hydroquinone and silver ions underlow light conditions^((24,25,32-37)). Acidic solutions of hydroquinoneand silver ions are metastable but spontaneous metal deposition isnormally very slow. The presence of metal catalysts (such as the silvernucleation sites on the DNA), significantly accelerates the process.Under these experimental conditions, metal deposition therefore occursonly along the DNA skeleton, leaving the passivated glass practicallyclean of silver. The process was terminated when the trace of the metalwire was clearly observable under a differential interference contrast(DIC) microscope. The metal wire followed precisely the previousfluorescent image of the DNA skeleton. The structure, size andconductive properties of the metal wire were reproducible and dictatedby the “developing” conditions.

Results:

Atomic force microscope (AFM) images of a section of a 100 nm wide, 12μm long wire are presented in FIGS. 15A and 15B. As clearly seen, thewire comprises 30-50 nm-diameter grains deposited along the DNAskeleton.

To study the electronic transport properties of these wires, twoterminal I-V curves have been measured at room temperature using an HPparameter analyzer with internal resistance of 10¹³ Ω and currentresolution of 10 fA. FIG. 16A shows the I-V curves of the silver wirepresented in FIGS. 15A and 15B. The curves are highly non linear andasymmetric with respect to zero bias. The shapes of the curves depend onthe voltage scan direction indicated by arrows in FIG. 16A. Approachingzero voltage from large positive or negative bias, the current vanishesalmost linearly with voltage. A zero-current plateau then develops withdifferential resistance larger than 10¹³ Ω. At higher bias, the wireturns conductive again with a differential resistance somewhat lowerthan in the original bias polarity. Repeated measurements in the samescan direction (solid curves in FIG. 16A) yield reproducible I-V curves.The length of the zero bias plateau in different wires can vary from afraction of a volt to roughly 10 volts. The solid line in FIG. 16Bdepicts, for example, the I-V curve of a different wire in which thesilver growth on the DNA was more extensive. As a result, the plateauwas reduced to 0.5 volts. By driving higher currents through the wire,the plateau could usually be eliminated to give an ohmic behavior(dashed line in FIG. 16B) with resistance varying between 1 and 30 MΩ,depending on the silver deposition process.

Example 10 Deposition of Gold on an Oligonucleotide Fiber

A gold enhancer can be used for enhancing nucleation centers ofpractically any metal.

A gold enhancer solution may be prepared as follows:

30 μl of KSCN solution (from a stock solution prepared with 60 mg ofKSCN dissolved in 1 ml H₂O) are added to 240 μl H₂O and thoroughlymixed. 30 μl of a KAuCl₄ solution (from a stock solution prepared bydissolving 23 mg of KAuCl₄ in 1 ml H₂O) are added to the KSCN solutionand mixed. Within several seconds the color changes from deep orange toa very light orange and then 60 μl hydroquinnon solution (from a stocksolution prepared by dissolving 55 mg hydroquinnon in 10 ml H₂O) areadded and the solution is thoroughly mixed.

The gold enhancer can be readily employed for gold growth on practicallyany metal. The growth rate can be tuned from 100 nm per few hours to 100nm per minute by replacing some of the water with a phosphate buffer,pH=8.

Example 11 Organic Conjugated-Polymer Based Conducting Wires

(i) The relevant part of the network is exposed to a solution containinga cationic segment capable of forming a conjugated-polymer by a chemicaltransformation or a cationic non conjugated-polymer capable ofundergoing conjugation by a chemical transformation or a cationicconjugated-polymer. Thus, ion exchange process occurs at the phosphategroups of the DNA skeleton exposed to the solution.

(ii) The ion exchanged DNA complex is treated according to the nature ofthe organic species that is bound to the polyanionic skeleton.Electrical functionalization is achieved either by the former process orby a sequential doping process. Doping may be achieved via conventionalredox processes, by protonation-deprotonation processes, byelectrochemical means or by photochemical means. Additionally, sequenceselective processes between the DNA skeleton and the building blocks ofthe above organic conjugated-polymer based conducting wires can beutilized for the production of wires with a well defined structure,electrical affinity gradients and p/n junctions.

I. The fabrication of a PPV (poly-phenylene vinylene) conducting wire isas follows:

(i) A DNA network fixed on a substrate is exposed to a solution of apre-PPV water soluble polymer. After the DNA polyelectrolyte isexchanged by the pre-PPV polymer, the substrate is rinsed carefully anddried.

(ii) The pre-PPV polymer loaded DNA network fixed on the substrate isreacted in a vacuum oven (e.g 1e-6 bar, 300 C., 6 hr.).

(iii) The resulting luminescent PPV polymer is doped using conventionalmethods until displaying conductivity.

II. An Alternative route for the fabrication of a PPV conductive wire isas follows:

(i) A DNA network fixed on a substrate is exposed to a solution of abis-(tetrahydrothiophenium)-p-xylilene dichloride. After the DNApolyelectrolyte is exchanged by thebis-(tetrahydrothiophenium)-p-xylilene dichloride, the substrate isrinsed carefully and dried.

(ii) The bis-(tetrahydrothiophenium)-p-xylilene dichloride loaded DNAnetwork fixed on a substrate is polymerized in a basic solution to forma pre-PPV polymer attached to the DNA backbone.

(iii) The pre-PPV polymer loaded DNA network fixed on a substrate isreacted in a vacuum oven (1e-6 bar, 300 C., 6 hr.).

(iv) The resulting luminescent PPV polymer is doped using conventionalmethods until displaying desired conductivity.

III. The fabrication of a PANI (polyaniline) conducting wire is carriedout as follows:

(i) A DNA network fixed on a substrate is exposed to a solution of anacid soluble PANI polymer. After the DNA polyelectrolyte is exchanged byPANI polymer, the substrate is rinsed carefully and dried.

(ii) The resulting PANI polymer is doped using conventional methodsuntil displaying desired conductivity.

IV. An alternative route to the fabrication of a PANI conducting wire isas follows:

(i) A DNA network fixed on a substrate is exposed to a solution ofanilinium ions. After the DNA polyelectrolyte is exchanged by theanilinium ion, the substrate is rinsed carefully and dried.

(ii) The anilinium ions loaded on the DNA skeleton are oxidized using asolution of an oxidizing agent such as peroxidisulphate ions, yielding apolyaniline polymer. The resulting PANI polymer is doped usingconventional methods until displaying desired conductivity.

V. An alternative route to the fabrication of a PANI conducting wire isas follows:

(i) A DNA network fixed on a substrate is exposed to a solution of ashort oligomer of PANI (>1 repeat unit). After the DNA polyelectrolyteis exchanged by the PANI oligomer, the substrate is rinsed carefully anddried.

(ii) The PANI oligomer ions loaded on the DNA skeleton are oxidizedusing a solution of an oxidizing agent such as peroxidisulphate ions,yielding a polyaniline polymer. The resulting PANI polymer is dopedusing conventional methods until displaying desired conductivity.

Example 12 Fabrication of Insulators

Insulators may be constructed on electrically functionalized parts ofthe network such as wires and connections between wires and components.

A. Insulation of Metallic Components (Including Metallic Wires):

(1) Metallic components may be electrically insulated from theirenvironment using surface active agents composed of an insulating bodysuch as an alkyl group attached to a surface binding group such as athiol or a disulfide group. The surface binding group binds to thesurface of the metal thus, forming a dense “two dimensional” layer ofelectrically insulating molecules at the surface of the metal. Thislayer presents an electrical barrier, namely, an insulator.

(2) The selective oxidation and other derivations that form nonconducting layers and interfaces form electrically insulating barrierstoo.

B. Insulation of Non Metallic Components (Including Conjugated-PolymerBased Wires):

Using complementary interaction based molecular recognition processes,insulating layers that can self assemble onto the surface of nonmetallic components are constructed. For example, positively chargedpolymers such as PANI can be coated and insulated from their environmentusing a polyanion polymer having long alkyl chain side groups.

Example 13 Attachment of a Gold-Containing Molecule or Particle to aSpecific Nucleotide

DNA bases are modified by attachment of a spacer arm connected to achemically active group to specific sites in the bases. For the rightsites and long enough spacer arms, such modifications do not interferewith the enzymatic machinery, leaving the DNA molecules compatible withthe recombinant DNA techniques. One such modification is the attachmentof biotin to a C or A base. At a next step, the specific binding ofstreptavidin to biotin is employed to the attachment of a streptavidincoated gold particle to the biotin label base. FIG. 17 shows an AFMimage of the result of such manipulation. In this case, the lastnucleotide in a long DNA molecule was replaced by a biotin labelednucleotide. The template was then immersed in a solution containingstreptavidin coated 5 nm gold colloids resulting in a specificattachment of these colloids to the modified bases. Since streptavidinhas four binding sites for biotin, the coated colloid can also serve asa junction between labeled DNA molecules. A junction between two DNAmolecules is also shown in FIG. 17. Groups other than biotin can also beused for labeling. Some examples include thiol, dig and amine.

Example 14 Preparation of a Single Electron Transistor (SET)

In the following the main steps in the fabrication of a SET areoutlined:

-   1. Substrate passivation is carried out according to Example 6.-   2. Gold electrode definition by standard microelectronic techniques    is carried out, e.g. as specified in Example 7. For the simple case    of a single SET only three electrodes are needed.-   3. Linker synthesis, e.g. carried out according to Example 1(a). The    Linkers are typically made of short (for example 12 bases)    olygonucleotides derivatized with a disulfide group at their 3′    side. For the case of a single SET, linkers with three different    sequences are preferable.-   4. Linkers are made to interact with the electrodes through their    disulfide group. Each electrode is marked by a different linker    according to Example 2.-   5. Three different disulfide derivatized linkers are attached to the    same nanometer scale gold particle at their disulfide side and one    of the linkers is attached via a large bridging agent which creates    a large barrier between the colloid and this linker.-   6. Three double-stranded DNA molecules, a few micron long,    containing sticky ends complementary to those of the linkers at the    gold particle are hybridized and ligated with the linkers attached    to the colloid to form a three terminal junction with the colloid at    the branching point. The three DNA molecules also contain sticky    ends complementary to the three linkers attached to the electrodes,    at their sides opposite to the gold particle.-   7. The network is completed by letting the double-stranded DNA    molecules attached to the gold particle to hybridize with the three    linkers on the electrodes, followed by ligation of the nicks.-   8. Electrical functionality is achieved by the following steps:    -   a) The gold particle is coated by an alkane thiol layer to be        used as an insulating barrier, and passivation layer against        metal deposition.    -   b) The DNA chains are coated with metal to form conducting        wires, for example as specified in Example 8. The wires are        electrically weakly coupled to the gold particle through the        alkane thiol layer insulating barrier with one wire coupled        through the large bridging agent having even weaker coupling to        the particle.    -   c) FIG. 6 outlines the final device composed of a gold particle        wired to three electrodes through the insulating barriers.

The current between two electrodes can now be modulated by a smallvoltage applied to the third electrode (the one very weakly coupled tothe particle). The circuit hence function as a SET. The SET can befabricated as a part of a more complex circuit where the electrodes arereplaced by functionalized network components.

It should be appreciated that the sequence of steps from the preparationof the SET may be altered, thus for example, step 6 may precede step 4,etc.

Example 15 PPV Functionalized Fiber as a Light Source

The process described in Example II may be followed up to and includingstep I(ii). The resulting PPV component is highly luminescent and has awidth considerably smaller than 100 nm. Fabricating the PPV componentbetween electrodes of appropriate work functions then forms anelectroluminescent device.

1. An electric network comprising: at least one nucleotide fibercomprising a chain of nucleotides and defining the networks geometry;and one or more substances, molecules, clusters of atoms or molecules orparticles bound to said nucleotide fiber or complexed therewithcontinuously along said fiber to form at least one electric orelectronic component or a conductor, the network being electricallyconnected to an electrically conducting interface component for electriccommunication with an external electric component or circuitry.
 2. Anetwork according to claim 1, wherein at least one of the networkcomponents is a wire.
 3. A network according to claim 1, comprising atleast two nucleotide fibers connected to one another at a junction inwhich one nucleotide segment of one fiber is bound to another nucleotidesegment of another fiber by a sequence-specific interaction.
 4. Anetwork according to claim 1, comprising a junction between a firstnucleotide fiber and a second nucleotide fiber, formed by a molecule,cluster of atoms or molecules or a particle bound to each of thenucleotide fibers.
 5. A network according to claim 1, comprising anentity being a molecule, cluster of atoms or molecules or a particle,which entity changes from an electrically conducting to an electricallynon-conducting state by transfer of electrons to or from said entity,wherein the entity is bound to one or more of the at least onenucleotide fiber.
 6. A network according to claim 1, comprisingnucleotides which have been chemically modified by attaching thereto asubstance molecule, cluster of atoms or molecules or particles.
 7. Anetwork according to claim 6, wherein the chemically modifiednucleotides are included in the network: (i) in junction betweennucleotide fibers for binding the nucleotide fibers to one another, (ii)in junction between a nucleotide fiber and a linker that binds anucleotide fiber to an electronic component of the network, or (iii) injunction between a nucleotide fiber or an electronic component and aninterface component.
 8. A network according to claim 6, wherein thechemically modified nucleotide carries one member of a binding couplefor binding to another component comprising the other member of thebinding couple.
 9. A network according to claim 6, wherein thechemically modified nucleotide carries a thiol, amine residue, an activeester or a carboxyl group.
 10. A network according to claim 1, having(a) at least one conductor being a wire constructed on a nucleotidefiber comprising at least one nucleic acid chain; (b) at least oneelectronic component being electrically connected to said at least onewire and being constructed either on a nucleic acid chain which has beenchemically or physically modified by depositing one or more molecules,cluster of atoms or molecules or particles thereon, or being constructedby a molecule, cluster of atoms or molecules or a particle situated at ajunction between two or more nucleic acid chains of different fibers.11. A network according to claim 1, comprising two or more nucleotidefibers assembled to form the network on the basis of sequence-specificinteraction of nucleic acid chains.
 12. A network according to claim 5,wherein at least one nucleic acid chain is formed into an electric orelectronic component by sequence or domain-specific binding thereto ofsaid substances, molecules, clusters of atoms or molecules or particles.13. A network according to claim 1, wherein at least one nucleotidefiber is made electrically conductive by substances comprising a metalbound to the nucleotide fiber or portion thereof.
 14. A networkaccording to claim 1, wherein the network comprises at least one wireformed by non-metallic conducting substance bound to a nucleotide fiberor portion thereof.
 15. A network according to claim 1, wherein at leastone nucleotide fiber has at least a portion bound to semi-conductingsubstances.
 16. A network according to claim 15, wherein the at least aportion, is a sequence within a nucleotide chain.
 17. A networkaccording to claim 1, wherein one of two adjacent portions of at leastone nucleotide fiber are bound to a p-type semi-conducting substance andthe other to an n-type semi-conducting substance, whereby the twoadjacent portions of the nucleotide fiber constitute a p/n junction. 18.A network according to claim 1, comprising at least one nucleotide-basedjunction formed by hybridization of complementary sequences ofnucleotide chains in at least two nucleotide fibers.
 19. A networkaccording to claim 18, wherein said junction is formed into bipolartransistors, comprising: (a) a p-type semi-conducting substance bound toa first nucleotide fiber at the junction and an n-type semi-conductingsubstance bound to adjacent, second nucleotide fiber at both sides ofthe first nucleotide fiber, or (b) an n-type semi-conducting substancebound to a first nucleotide fiber at the junction and a p-typesemi-conducting substance bound to adjacent, second nucleotide fiber atboth sides of the first nucleotide fiber.
 20. A network according toclaim 1, comprising at least one input/output interface componentconnected to at least one network component in a manner allowingelectric conductivity between said interface component and said networkcomponent.
 21. A network according to claim 20, comprising at least twointerface components, each one connected to at least one nucleotidefiber or electronic component of the network.
 22. A network according toclaim 20, wherein said interface component is connected to a wire, saidwire comprising a nucleotide fiber.
 23. A network according to claim 22,wherein the nucleotide fiber has a nucleotide end segment, and is boundto the interface component by a specific interaction with a complexingagent bound to a linker attached to the interface component.
 24. Anetwork according to claim 23, wherein the linker comprises a nucleotidechain, and said nucleotide end segment is bound thereto bysequence-specific interaction.
 25. A network according to claim 20,wherein said interface component is bound to a nucleotide fiber that isbound to an electronic component of the network.
 26. An electroniccircuit comprising a network according to claim
 1. 27. A method formaking an electronic network, comprising: (a) providing an arrangementcomprising at least one electrically conductive interface component; (b)attaching a linker to the at least one interface component; (c)contacting said arrangement with at least one nucleotide fibercomprising a chain of nucleotides and defining the network's geometry,with a sequence capable of binding to the linker, and permitting bindingof said sequences to said linker; and (d) electrically or electronicallyfunctionalizing the at least one nucleotide fiber by depositing thereonor complexing thereto at least one substance or particles.
 28. A methodaccording to claim 27, wherein the network is formed by self-assembly asa result of chemical complementary and molecular recognition propertiesof at least one nucleotide fiber to at least one other nucleotide fiberor between at least one nucleotide fiber and at least one specificsequence or domain-recognizing complexing agent.
 29. A method accordingto claim 27, comprising mixing nucleotide fibers and components togetherand allowing them to self-assemble into a network by means of specificmolecule interactions.
 30. A method according to claim 27, comprisingforming junctions between nucleotide fibers and at least one molecule,cluster of atoms or molecules or particles, said molecule clusters orparticles serving as an electronic component in the network.
 31. Amethod according to claim 27, wherein said functionalization is achievedby forming on said nucleotide fiber at least one nucleation center fromwhich said substance or particles are grown.